The Ischemic Heart SCOR at The University of Texas Southwestern Medical Center at Dallas will continue research directed at elucidating pathophysiological mechanisms operative during myocardial ischemia and evolving myocardial infarction. Research work in this SCOR is built upon the principle that from the elucidation of fundamental mechanisms responsible for myocardial ischemia and its consequences will come improved patient care and rehabilitation, and the ability to prevent myocardial infarction in some individuals at risk. The experimental studies that we have proposed represent continuations of productive research efforts that have been ongoing within this Program during the previous 14-1/2 years. However, 4 new research sections have been added to the Clinical Section (Project 2) of our Ischemic SCOR Program, including new studies that will elucidate mechanisms responsible for fish oil diets reducing the risk of restenosis after coronary angioplasty; studies that will demonstrate whether serotonin and thromboxane accumulation at sites of coronary artery injury and stenosis are important physiologically in altering coronary vascular resistance and flow; and studies that will help develop nuclear magnetic resonance (NMR) imaging and spectroscopy for the noninvasive detection of myocardial ischemia and to estimate perfusion, evaluate segmental and global ventricular function, and detect atherosclerotic plaques. In addition, new research studies have been added that will utilize molecular biology methods to: (a) evaluate gap junction proteins and their role in the regulation of cell-to-cell communication and calcium binding and determine how their function is altered with ischemic cell injury (Project 8) and (b) study the interaction between tissue plasminogen activator and its endogenous inhibitor and develop mutant tissue plasminogen activators that may be evaluated in relevant animal models (and later patients) for their thrombolytic potential (Project 9). A new research section that will evaluate basic mechanisms contributing to the development of congestive heart failure has also been added (Project 10). We have also added new research studies to evaluate the role of proteases in myocyte and vascular injury (Project 7) and study the effects of myocardial ischemia on the cardiac microcirculation (Project 4). Coronary heart disease remains a major health hazard in contemporary western society. This Ischemic SCOR Program has been productive and made important contributions toward: (a) the elucidation of basic pathophysiologic mechanisms involved in the evolution of cellular and vascular damage during myocardial ischemia and infarction; (b) the development of sensitive methods for the identification of acute myocardial ischemia and infarction and estimating their extent; and (c) providing improved prognostic insight so that selected patients at risk for future ischemic heart disease complications may be identified prior to their development.